Atopic dermatitis (AD) is a common manifestation of the allergic phenotype. Characterized by erythema,[unreadable] pruritis, swelling and hives, Atopic Dermatitis can be an early indicator of subsequent atopic phenotypes. At[unreadable] least half of infants diagnosed with Atopic Dermatitis will develop subsequent atopic disease, such as[unreadable] eosinophillic esophagitis, food allergy, allergic rhinitis and allergic asthma. However, the pathogenesis of[unreadable] Atopic Dermatitis and the contribution of this condition to subsequent allergic phenotypes are still largely[unreadable] unclear. Th2 cells, T cells that secrete IL-4, IL-5, IL-13 and other cytokines are critical in the development of[unreadable] atopic diseases. IL-4 promotes the development of Th2 cells by activation of the Signal Transducer and[unreadable] Activator of Transcription State. Mice deficient in State have a general decrease in Th2 immunity and in[unreadable] models of asthma and eosinophilic esophagitis have greatly diminished disease. Increased levels of Th2[unreadable] responses are often associated with the development of Atopic Dermatitis. However, the lack of a model of[unreadable] Atopic Dermatitis that is strictly dependent upon Th2 immunity has hampered a more detailed analysis of[unreadable] Th2 cells in AD. We have recently developed transgenic mice expressing a constitutively active State[unreadable] (Stat6VT) in T cells resulting in a hyper-Th2 phenotype. These mice are prone towards developing an[unreadable] Atopic Dermatitis phenotype in a specific pathogen free environment. Moreover, Stat6VT transgenic mice[unreadable] on an IL-4-deficient background do not develop disease, supporting the requirement forTh2 immunity in this[unreadable] model. The overall goal of this project is to determine the role of Th2 effector cytokines in a model of Atopic[unreadable] Dermatitis and determine how, in both patient samples and in our mouse model, Atopic Dermatitis[unreadable] pathogenesis affects immune responses and might contribute towards the development of subsequent[unreadable] atopic diseases. Our hypothesis is that a Th2 skewed immune response is predisposed towards atopic[unreadable] dermatitis and increases the risk of subsequent allergic responses. This will be tested in three Aims: 1,[unreadable] Define cytokine secretion and State activation in specific T cell populations from infants with Atopic[unreadable] Dermatitis; 2, Define the effectors required for the development of Atopic Dermatitis in StatBVT transgenic[unreadable] mice; and 3, Define the role of Atopic Dermatitis in predisposition towards subsequent atopic diseases using[unreadable] animal models. The results of these Aims will better define the role of Th cells in the generation of Atopic[unreadable] Dermatitis and subsequent allergic diseases.